Strong sonic hedgehog signaling in the mouse ventral spinal cord is not required for oligodendrocyte precursor cell (OPC) generation but is necessary for correct timing of its generation

Hashimoto, H; Jiang, Wen; Yoshimura, Takeshi; Moon, Kyeong-Hye; Bok, Jinwoong; Ikenaka, Kazuhiro

doi:10.1016/j.neuint.2017.11.003

Cited by 14 publications

(11 citation statements)

References 44 publications

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“…Cai et al corroborated these findings in vivo demonstrating Nkx6- and Shh -independent generation of an OPC subpopulation, which suggests the involvement of other molecular pathways [26]. Indeed, Shh is important for the timing of OPC generation as a recent study has shown [42].…”

Section: Oligodendrocyte Progenitor Cells (Opc) and Oligodendrocytmentioning

confidence: 82%

Oligodendrocytes in Development, Myelin Generation and Beyond

Kuhn

Gritti

Crooks

et al. 2019

Cells

409

263

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Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer’s disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes.

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Section: Oligodendrocyte Progenitor Cells (Opc) and Oligodendrocytmentioning

confidence: 82%

Oligodendrocytes in Development, Myelin Generation and Beyond

Kuhn

Gritti

Crooks

et al. 2019

Cells

409

263

View full text Add to dashboard Cite

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“…The Hedgehog signaling pathway plays a significant role in mammalian development, is involved in the regulation of cell proliferation, survival, and differentiation[102,103], and is responsible for the formation of the neural tube, axial bone, hair, and teeth[104-106]. The Hedgehog gene is inhibited in most adult tissues and involved in the maintenance and repair of only certain tissues.…”

Section: Csc Signaling Pathways and Inhibitorsmentioning

confidence: 99%

Targeting cancer stem cells in drug discovery: Current state and future perspectives

Zhou

Sun

et al. 2019

WJSC

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In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways ( e.g ., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication, survival, and differentiation. Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape. Therefore, multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs. Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials, and some inhibitors, such as vismodegib, sonidegib, and glasdegib, have been approved. Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein. The signal transducers and activators of transcription 3 (STAT3) inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers. Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development, which is another strategy for CSC therapy. In addition to the potential pharmacological inhibitors targeting CSC-related signaling pathways, other methods of targeting CSCs are available, such as nano-drug delivery systems, mitochondrion targeting, autophagy, hyperthermia, immunotherapy, and CSC microenvironment targeting. In addition, we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.

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“…Shh activity is necessary for the establishment of the pMN domain and motor neuron formation, and subsequently, a transient increase in Shh activity coincides with, and is required for, timely OPC specification (Danesin and Soula, 2017). Pharmacological and genetic reduction of Shh signaling in chick, mouse and zebrafish spinal cords results in prolonged motor neuron formation and impaired OPC formation (Al Oustah et al, 2014;Danesin et al, 2006;Hashimoto et al, 2017;Jiang et al, 2017;Ravanelli and Appel, 2015;Touahri et al, 2012). Furthermore, in chick neural tube explants treated with exogenous Shh, premature formation of OPCs occurs at the expense of motor neurons (Danesin et al, 2006;Orentas et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating Shh signaling response

et al. 2020

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Spinal cord pMN progenitors sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Some OPCs differentiate rapidly as myelinating oligodendrocytes, whereas others remain into adulthood. How pMN progenitors switch from producing motor neurons to OPCs with distinct fates is poorly understood. pMN progenitors express prdm8, which encodes a transcriptional repressor, during motor neuron and OPC formation. To determine whether prdm8 controls pMN cell fate specification, we used zebrafish as a model system to investigate prdm8 function. Our analysis revealed that prdm8 mutant embryos have fewer motor neurons resulting from a premature switch from motor neuron to OPC production. Additionally, prdm8 mutant larvae have excess oligodendrocytes and a concomitant deficit of OPCs. Notably, pMN cells of mutant embryos have elevated Shh signaling, coincident with the motor neuron to OPC switch. Inhibition of Shh signaling restored the number of motor neurons to normal but did not rescue the proportion of oligodendrocytes. These data suggest that Prdm8 regulates the motor neuron-OPC switch by controlling the level of Shh activity in pMN progenitors, and also regulates the allocation of oligodendrocyte lineage cell fates.This article has an associated ‘The people behind the papers’ interview.

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Strong sonic hedgehog signaling in the mouse ventral spinal cord is not required for oligodendrocyte precursor cell (OPC) generation but is necessary for correct timing of its generation

Cited by 14 publications

References 44 publications

Oligodendrocytes in Development, Myelin Generation and Beyond

Oligodendrocytes in Development, Myelin Generation and Beyond

Targeting cancer stem cells in drug discovery: Current state and future perspectives

Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating Shh signaling response

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